Hong-Ji Xu, M.D., Ph.D. The research of my laboratory focuses on
searching for novel therapeutic genes for human cancer as well
as applying knowledge about tumor suppressor genes and cytokine
genes to the design of cancer gene therapy. The strengths of
our comprehensive and dynamic research program lie in the novelty
of its research. We are the first to successfully construct
a single recombinant adenovirus vector that directs high-level
and tetracycline-regulatable expression of human cytokines in
a variety of human cells. Although further obstacles are to
be circumvented, we believe that the availability of this type
of vector may help to pave the way for predictable and controllable
gene delivery. I am the primary inventor of 4 patents awarded
or pending, including one pertinent to an N-terminal-truncated
RB tumor suppressor gene for anticancer therapy (U.S. patent
5,496,731, 1996).

Our basic research is centered on the mechanisms
of differential induction of apoptosis and senescence following
expression of potential therapeutic genes in tumor cells. Recent
studies done by us have also provided direct evidence for pRB-mediated
cellular senescence and inhibition of telomerase activity. Thus,
overexpression of pRB protein in tumor cells is sufficient to
reverse their immortality, while the replicative life spans
of normal cells are not affected. In this connection, we have
committed ourselves to a phase I prostate cancer gene therapy
clinical trial using a modified RB tumor suppressor gene. The
clinical trial will take place at the Department of Genitourinary
Medical Oncology with Dr. Christopher Logothetis as principal
investigator of the clinical protocol. In a pilot project, we
shall be able to generate preliminary data to support a new
approach to cytokine gene-mediated in situ tumor vaccination
for advanced cancers using transcriptionally targeted and regulatable
vectors.